MOTS-c — Compound Reference

Compound Reference Log · Deep Dive

MOTS-c

A short mitochondrial-derived peptide encoded within mitochondrial DNA, studied as a research signal in cellular metabolism and stress response.

Mitochondrial-derived peptide16 amino acidsEncoded in mitochondrial 12S rRNAResearch use only
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01

What the name means

MOTS-c stands for Mitochondrial ORF of the Twelve-S rRNA type-c. The name is a literal description of where its coding sequence sits — an open reading frame (ORF) hidden inside the mitochondrial 12S ribosomal RNA gene.

Unlike the coded compounds elsewhere in this log, MOTS-c is a real research name that decodes directly to its genomic origin.

02

What it actually is

MOTS-c is a small mitochondrial-derived peptide (MDP) of 16 amino acids. It is notable because it is encoded not in the cell nucleus but within mitochondrial DNA.

Type Mitochondrial-derived peptide (MDP)

Length 16 residues

Bonds Short linear peptide

Origin Mitochondrial 12S rRNA open reading frame

Its small size and mitochondrial genomic origin place it in a distinct family from the nuclear-encoded and engineered peptides catalogued elsewhere in this log.

03

Where it came from

MOTS-c was identified by researchers studying hidden coding sequences in the mitochondrial genome — work associated with the laboratory of Pinchas Cohen and colleagues (including Changhan Lee) at the University of Southern California, reported around 2015.

The finding was part of a broader recognition that the small mitochondrial genome encodes short bioactive peptides beyond its well-known respiratory-chain proteins.

04

Why it was created — the thought process

MOTS-c was not designed — it is a naturally occurring peptide. The research interest is in what it may signal: mitochondrial-derived peptides are studied as messengers that let mitochondria communicate with the rest of the cell about metabolic and stress states.

Investigators have examined MOTS-c in the context of pathways such as AMPK-related metabolic signaling. This log notes that as an area of study, not as an established function or benefit.

05

How it is made

For research use, MOTS-c is produced by solid-phase peptide synthesis: the 16-residue chain is assembled on a resin, then cleaved, purified by HPLC, and confirmed by mass spectrometry.

Its short linear structure makes it a straightforward synthetic target, so laboratory material does not require recombinant expression.

06

What the research actually shows — honestly

What has been studied for MOTS-c is its role as a mitochondrial-derived signaling peptide and its association with metabolic pathways in cell and animal models — described here as mechanism, not outcome.

This is research-use-only content. It makes no health or benefit claims and provides no dosing, timing, or protocol. Much of the evidence base is preclinical; findings in models are not proof of human effects. For specifics, consult a physician and the primary literature.

07

Selected research & sources

The items below are drawn from the peer-reviewed literature (PubMed) and describe results observed in research models or reported in the clinical literature. They are listed so the evidence can be examined at its source — not to suggest any use.

  1. Zheng Y, Wei Z, Wang T. Front Endocrinol. 2023. “MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation.” doi.org/10.3389/fendo.2023.1120533
  2. Lee C, et al. Cell Metab. 2015. “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” doi.org/10.1016/j.cmet.2015.02.009
  3. Lee C, Kim KH, Cohen P. Free Radic Biol Med. 2016. “MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism.” doi.org/10.1016/j.freeradbiomed.2016.05.015
  4. Yin Y, et al. Pharmacol Res. 2021. “MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.” doi.org/10.1016/j.phrs.2021.105987
  5. Yin Y, et al. Adv Sci. 2024. “MOTS-c Suppresses Ovarian Cancer Progression via USP7/LARS1.” doi.org/10.1002/advs.202405620

Regulatory status: Not an approved drug. Research material, RUO.

◆ A reference, not a recommendation

This page explains what MOTS-c is and where it came from — the science and the story — not who should use anything, or how. These are research materials for laboratory research only; nothing here is medical, dosing, or treatment advice.

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Compound Reference Log · MOTS-c
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